The overall goal of this project is to demonstrate the ability of the beta2-adrenoceptor agonist, clenbuterol, and adult stem cell transplantation in combination to oppose irreversible loss of locomotor function due to contusion, the most common type of spinal cord injury (SCI). At present, only methylprednisolone has been shown to have efficacy in humans for SCI However, the extent of recovery is limited so that additional or alternative treatments are needed. Potentially superior countermeasures are available, but require a demonstration of efficacy in an appropriate animal model of spinal cord contusion injury prior to use in patients. The proposed studies are an outgrowth of previous work in which Beta2-agonists or transplantation of adult pluripotent stem cells into the contusion site enhanced recovery of locomotor function following SCI in rats. Recovery of locomotor function, in turn, correlated with sparing of myelinated white matter and successful transplantion. We will determine the efficacy of clenbuterol and stem cell transplantation used in combination for sparing and regenerating spinal cord tissue and improving locomotor function following contusion in an established model of SCI developed by the Multicenter Animal Spinal Cord Injury Study (MASCIS). Optimization of Beta2-agonist treatment and stem cell transplantation into the contused spinal cord may lead to a therapeutic modality for SCI. PROPOSED COMMERCIAL APPLICATION: This project will lead to a treatment for spinal cord injury based on activating stem cells directly or indirectly with clenbuterol after injection of the stem cells into the injury site. The method will be patented, licensed and marketed as a new therapy.